Epithelial cell adhesion molecule (EpCAM; CD326) is a type I membrane protein that has been reported as a cancer-specific cell surface antigen expressed in colorectal cancer (Non Patent Literature 1). EpCAM is expressed mainly on the basal membranes of epithelial cells in normal tissues. However, because its expression is observed in most of cancer cells of epithelial origin, EpCAM has been known as a so-called cancer antigen and has been shown to be useful as a diagnostic marker (Non Patent Literature 2).
As the sensitive techniques to detect cancer cells have been established in recent years, it has been found that tumor cells exist and circulate in blood: circulating tumor cells. The presence of the circulating tumor cells is closely associated with metastasis of cancer and is therefore very important for prognostic prediction. Since EpCAM is detected in most of cancer cells of epithelial origin, as mentioned above, prognostic prediction by a method which involves collecting cells having the EpCAM antigen on their surface with an antibody and detecting this antibody has already been practiced (Patent Literature 1).
It has also been shown that EpCAM dissociate from the surface of tumor cells to increase significantly its concentration in the serum of malignant tumor patients, suggesting that EpCAM can be used not only as a surface marker of tumor cells but as a tumor marker in serum.
Furthermore, in addition to its diagnostic benefit, the therapeutic benefit of EpCAM has been shown in recent years. Cancer vaccines have already been developed by use of EpCAM, and vaccine therapies have also been reported, in which EpCAM proteins prepared with an insect cell expression system such as a baculovirus system, or anti-idiotype antibodies binding to the antigen recognition site of an anti-EpCAM antibody are used. In addition, anti-EpCAM antibodies for cancer treatment have also been developed, and clinical trials are underway using anti-EpCAM antibodies such as Adecatumumab (MT201) and ING-1. The treatment using these antibodies is intended to reduce the size of tumor by cellular immunity (cytotoxic activity) induced by binding of the antibody to EpCAM on the surface of tumor cells through the patient's own immune system. For the purpose of enhancing the cytotoxic activity of the anti-EpCAM antibodies, Proxiniums Vivendiums (VB4-845) which is an anti-EpCAM antibody fused with a pseudomonas exotoxin, EMD 273 066 (huKS-IL2) which is an anti-EpCAM antibody fused with IL-2, EU-approved Catumaximab which also has anti-CD3 activity, and the like have been further developed (Non Patent Literatures 3 and 4).
As mentioned above, EpCAM is very important for the diagnosis, prognostic prediction, and treatment of cancer, and the efficacy of molecules specifically binding to EpCAM, such as antibodies, in the diagnosis and treatment of cancer have been established. In addition to the antibodies mentioned above, α-actinin, claudin 7, CD44v4-v7 (a splicing valiant of CD44), D6.1A protein (a kind of tetraspanin), and the like are known as the molecules that bind to EpCAM specifically (Non Patent Literature 5).